JPS59141587A - Manufacture of organic germanium propionic acid derivative - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing mr rumanium propionic acid derivatives from germanium tetrachloride.

Kei Asai and others have reported that germanium chloroform (HGe (J3) reacts with acrylonitrile or acrylic acid to produce the following remarkable pharmacological effects, ta+ Fihrich ascites).
stumour) (U.S. Pat. No. 3,689)
, No. 516, K. Asai, September 5, 1972 λtb+ Rat ascites liver gaff
epatoma) AH44 and AH66, and AC
Treatment and lifespan extension effect on Erat BC47 tumor, Icl hypertension treatment (U.S. Pat. No. 3,793,455, K. Asai et al., February 19, 1974), (a+ U Onset of starch disease (amyloiclosi)
It is a product that has been proven to suppress infection caused by viral pathogen cells and protozoa, (el) to promote the growth rate of plants, (gl) to treat various diseases during clinical tests. It was found that bis-β-carboquine sesquioxide ethyl gelmanilamura can be produced.

In the prior art, propionic derivatives of kermanium sesquioxide have been described in the following systems (US Pat. No. 3,689,516 and No. 6,793,455, Japanese Pat. No. 46
Specification No. 2498, Nihon Gaishi Co., Ltd., 1974
All these methods use HGeC13 as the source material for germanium, which is usually expressed as: (al Ges + HCJl, −〉HGeCJ
3(bl Ge(OH)2+H'J->HGeCf3
[0) GeCJ2 + HCJ-->HGe(J3
Generate it like this.

The germanium compounds used in the above method are inherently unstable and therefore difficult to handle.

Result - HGeCJ! 3 is not readily available for use.

Ung Soo Pahk
suggested the production of bis-β-carboquine ethyl germanium sesquioxide from germanium dioxide (U.S. Pat. No. 3,812,167, May 21, 1974).
Day). In this method, GeO2+ H(J □→ GeCJ-4G e C
14+ N a H2P O4-111 → HGeC
J3HGeC23+ NH40H-m--→ G e
(OH) 2↓Go(OH)z +H(J,
HGeC13HGe (J3 + 0H2=OHON
-〉CJsGeC! Includes H3OH2ON.

However, it has been observed that the above reaction cannot produce the compound since -basic sodium phosphate does not have the potential to reduce germanium dioxide.

It is therefore an object of the present invention to overcome the drawbacks of the above-mentioned methods by making effective use of commonly and easily available raw materials. In the method of the invention, germanium tetrachloride is reduced with hypophosphorous acid or a salt thereof in the presence of hydrochloric acid, or a lower alcohol or lower alcoholic hydrochloric acid. This is then reacted neat with an acrylic type derivative followed by hydrolysis to form an organogermanium zolopionic acid derivative.

In the first step of the process of the invention, germanium tetrachloride in a lower alcohol or hydrochloric acid solution is readily reduced with hypophosphorous acid to a mixture of rrumanium sulfite and germanium chloride. The present invention uses a primary germanium compound and hydrochloric acid in an aqueous solution and/or a water-miscible lower alcohol solution. The reactants thus formed tend to react with the acrylic derivative,
A mixture of organic delmanochloride and organic rlumanophosphite is produced. The reaction mixture is as follows (wherein, Y is coo
3 (!OORCR is lower alkyl), 0ONH
or ON, and RIA and R2 are unrelated to each other and represent hydrogen or lower alkyl), and can be hydrolyzed as is to produce organogermanium sesquioxide derivatives.

Therefore, in the present invention, in order to produce an organogermanium sesquioxide derivative of the following formula (2) (wherein R1 and R2 are hydrogen or lower alkyl, irrespective of each other), step (1) germanium tetrachloride is carried out. by reacting it with hypophosphorous acid (added as such or generated in situ from its salts under the action of hydrochloric acid and/or lower alcohols), 11) Thereafter, the following formula (1) [
where R1 and R2 are as defined above, and Y is 0OOH, 0OOR (R is lower alkyl),
0ONH2 or ON], and the product of step (11) is hydrolyzed to form the formula (2).
The object of the present invention is to provide a manufacturing method comprising: producing the compound.

The lower alcohol used in step (1) is usually 01-C3
It's alcohol. This step is suitably carried out at an elevated temperature, for example at reflux temperature. There are no special temperature requirements for steps (11) and 1iil; ambient temperature is sufficient.

However, higher or lower temperatures may be used if desired.

Other useful groups for R1 and R2 include phenyl, furfuryl, thiophenyl, gyridyl and derivatives thereof.

The following examples will serve to further explain the practice of the invention. In Examples 1 to 7, H
Using sodium hypophosphite dissolved in CJ medium,
Reduces germanium tetrachloride. Example 8 to Example 1
Up to 4, germanium tetrachloride is reduced in an aqueous hypophosphorous acid solution. Examples 15 to 19 use sodium hypophosphite dissolved in methanol for the reduction step. In Examples 20 to 26, the reduction is carried out with aqueous hypophosphorous acid dissolved in methanol.

Example 24 uses hypophosphorous acid dissolved in ethanol, Example 25 uses hypophosphorous acid and acidic ethanol, and Example 26 uses sodium hypophosphite with ethanol. , Example 27 uses sodium hypophosphite and acidic ethanol. If using aqueous hypophosphorous acid itself, then H (J and/or
It may be preferable in some cases to add alcohol.

Hypophosphorous acid can be generated in situ with hypophosphite using hydrochloric acid [and/or ethanol].

In any case, even if hypophosphorous acid itself is used, the presence of hydrochloric acid is preferred since it speeds up the reaction and increases the yield.

Example 1 tal Reduction of Ge(J4) with sodium hypophosphite, 420 g of Ge(J) is added to a solution of 60 y of sodium hypophosphite in concentrated H(Jroom). Heated at reflux for 1 hour then cooled. Bring to room temperature. Save the reduction mixture for later use.

(b+ Bis-β-carboxyethyl dermamanium sesquioxide production from acrylic acid, 6.5 g of acrylic acid was added at room temperature to the G produced in step (al).
e (J4 is added to the reduction mixture. After reacting for 4 hours with stirring, the separated solid is collected by filtration.

The solid is dissolved in 70 ml of water and stirred for 1 hour at room temperature for hydrolysis. The crystals are collected by filtration and washed sequentially with water and acetone. Open (80°C~1
00 °C) to give 8 g (yield 50 °C) of the title compound.
%).

In the infrared spectrum of the product, the characteristic of 0OOH is 3.
300crn-1~2800cm-1,1690cm
-'', 1410 cm-'', 1240 cm-', and 900 cm-'' and 8[
It shows absorption at 10 cm-1. The spectrum is based on Asai's book [Organic Rumanium - God's Gift Medicine (Org.
anic()ermanium-A Medical
It is exactly the same as the infrared spectrum described in Godsend) J (Japanese board), and it is also
It also matches a commercially available sample that can be purchased from Asai C11nic.

The magnetic resonance spectrum (D20, Na0D) shows 1
The triplet maxima of the same number of protons are shown at ゜6 and 2.5 pharynges.

Elemental analysis of Ge - theoretical value 42.6, actual value 41.
8%.

Example 2 Bis-β-carboxy β sesquioxide from methacrylic acid
- Preparation of methyl ethyl germanium 8 g of methacrylic acid are added at room temperature to the G eC,I-4 reduction mixture produced in step (a) of Example 1. After reacting for 4 hours with stirring, the separated solids are collected by filtration. The solid was hydrolyzed as in the step of Example 1 (bl) to give 10 g of the title compound (yield 58
%).

In the infrared spectrum, 3450 C-m”.

6600cm-1~28ooCm-1,1700m-1
, 141-Oc1n21.1240cm-1 C0OH
The absorption characteristic of 880cm” and 800cm
-” indicates absorption, which is a characteristic of germanium sesquioxide.

Nuclear magnetic resonance spectrum (D20, Na0D) shows maxima at 1.2 lord (d, 3H), 1.6 ppm (q, 2H) and 2.8 ppill (m, IH,).

Example 6 Preparation of bis-β-carboxy-β-methyl ethyl germanium sesquioxide from methyl methacrylate. 9.6y of methyl methacrylate is added at room temperature to the GeCJ4 reduction mixture produced in the step of Example 1 (al). .

After reacting for 4 hours with stirring, the oily product is extracted with benzene. After evaporating off the benzene, the residue is dissolved in 70 ym of water and stirred for 1 hour at room temperature for hydrolysis. The crystals are collected by filtration and washed sequentially with water and acetone. Oven (80℃~
100 °C) to give the title compound 5.5 N C
A yield of 62 cm) was obtained.

The infrared spectrum is exactly the same as the product of Example 2.

Example 4 Preparation of bis-β-carboxyethyl germanium sesquioxide from methyl acrylate, methyl acrylate 8I
Ge(J4) produced in step (a) of Example 1 at room temperature.
Add to the 4-return mixture. After allowing the reaction to proceed for 4 hours with stirring, the oily product is extracted with benzene. After the benzene was removed by evaporation, the residue was processed into Example 6.
Hydrolyze as before. Filtration collects 7 g (yield: 46 g) of solid bis-β-carboxyethyl manium sesquioxide. The infrared spectrum is exactly the same as that produced in Example 1 fl)].

Example 5 Bis-β-carboxine-α- sesquioxide from crotonic acid
Preparation of methyl ethyl germanium. Add 8 g of crotonic acid at room temperature to the GeCJ4 reduction mixture produced in step (al) of Example 1. Allow to react for 4 hours with stirring and then collect the solid by filtration. Example The solid is hydrolyzed with water as in step (b) of 1 to give the title compound 8.5I (50% yield).

In the infrared spectrum 3300 cIn-' ~ 280
0cm”, 1695cm-1, 1410C1n-1,
1250cm” has the characteristic absorption of 000H, and 90
At 0 cm'' and 790 cm'', absorption characteristic of germanium sesquioxide is shown.

Example 6 Preparation of bis-β-carboxyethyl germanium sesquioxide from acrylonitrile, acrylonitrile 4.
9I at room temperature, Ge(
Add to J44 recycle mixture.

After 4 hours of reaction with stirring, the oily product is extracted with benzene. After removing the benzene by evaporation,
50 ml of concentrated hydrochloric acid is added to the residue, heated under reflux for 1 hour, further diluted with 100 ml of water, and then cooled to room temperature.

Collect the generated precipitate and wash it sequentially with water and acetone,
Drying yields the title compound 1' (25% yield). The infrared spectrum is exactly the same as that produced in step fbl of Example 1.

Example 7 Bis-β-carboxine sesquioxide from acrylamide
Add ethyl germanium, acrylamide 51, at room temperature to the Ge(J,4 reduction mixture produced in step (a) of Example 1. Allow to react for 4 hours with stirring. Collect the solid by filtration and concentrate. After heating under reflux with hydrochloric acid, hydrolyzing it in water as in Example B,
Title compound 5. F (yield: 60 cm) is obtained. The infrared spectrum is exactly the same as that produced in the process of Example 1 (bl).

Example 8 +a+ Preparation of GeCJ4 reducing solution by reducing GeCl4 with a 50% aqueous solution of hypophosphorous acid, Ge(4
420El is added to 38 g of a 50% aqueous solution of hypophosphorous acid. The reaction mixture is heated to reflux for 1 hour and cooled to room temperature for later use.

(b) Production of bis-β-carboquine ethyl germanium sesquioxide from acrylic acid. Add 6.5y of acrylic acid at room temperature to the Ge(J, reduction mixture produced in step ta+ above). React for 4 hours with stirring. After cooling, the separated solid is collected by filtration. The solid is hydrolyzed as in step tb) of Example 1 to give the title compound 71 (45% yield). The infrared spectrum is exactly the same as that produced in the process of Example 1 (bl).

Example? Bis-β-carboxy-β sesquioxide from methacrylic acid
- Preparation of methyl ethyl germanium. Methacrylic acid 81 is added at room temperature to the GaCl2 reduction mixture produced in step fa) of Example 8. After reacting for 4 hours with stirring, the separated solids are collected by filtration. As in the process of Example 1 (bt), the solid was hydrolyzed in water to give the title compound 8.5 f!
A yield of 50 cm) is obtained. The infrared spectrum is exactly the same as that produced in Example 2.

Example 10 Preparation of bis-β-carboxy β-methyl ethyl germanium sesquioxide from methyl methacrylate. do.

After 4 hours of reaction with stirring, the oily product is extracted with benzene. After removing the benzene by evaporation, the residue is hydrolyzed in water as in Example 6 to obtain the title compound 4.2 F (25% yield). The infrared spectrum is exactly the same as that produced in Example 2.

Example 11 Preparation of bis-β-carboxyethyl germanium sesquioxide from methyl acrylate.
Add to reduction mixture. After 4 hours of reaction with stirring, the oily product is extracted with benzene. The benzene is removed by evaporation and the residue is hydrolyzed in water as in Example 6 to give the title compound 10F.

The infrared spectrum is exactly the same as that produced in step [bl] of Example 1.

Example 12 Bis-β-carboxy-α- sesquioxide from crotonic acid
Preparation of Methyl Ethyl Germanium To the GeCJ-, reduction mixture produced in step ta+ of Example 8, 8 g of crotonic acid is added at room temperature. After reacting for 4 hours with stirring, the separated solids are collected by filtration. The solid was hydrolyzed in 1 water as in step (b) of Example 10, and the infrared spectrum was as shown in Example 5.
5 g (yield 30 g) of the title compound are obtained which is exactly the same as that produced in .

Example 16 Preparation of bis-β-carboquine ethyl germanium sesquioxide from acrylonitrile, process of Example 8 fat
4.9 I of acrylonitrile is added to the GeCt produced in the reduced mixture at room temperature.

After 4 hours of reaction with stirring, the oily product is extracted with benzene. The solvent was concentrated and removed, and the residue was hydrolyzed with concentrated hydrochloric acid and further diluted with water as in Example B, so that the infrared spectrum was exactly the same as that produced in step fbl of Example 1. Compounds with the same title 5.
F (yield: 61 cm) was obtained.

Example 14 Bis-β-carboxy sesquioxide from acrylamide
Preparation of Ethyl Germanium, Ge(J4) produced in step ta+ of Example 8, acrylamide 5,9 is added to the reduction mixture at room temperature. After reacting for 4 hours with stirring, the separated solid is collected by filtration. As in Example 6, the solid was hydrolyzed by refluxing with concentrated hydrochloric acid and further diluted with water so that the infrared spectrum was exactly the same as that produced in the step of Example 1 (bl). The title compound 6°8.9 (yield 24°) is obtained.

Example 15 (al Production of menolic germanium solution, Ge
(Dissolve 2 g of 449° in 73 m of methanol.

100 ml of methanol containing 9y of sodium hypophosphite are added to this solution. After reacting for 1 hour with stirring, the formed NaCJ is separated and the filtrate is saved for later use.

(bl Production of bis-β-carboxyethyl kermanium sesquioxide from acrylic acid, the above steps ta
Add 7 g of acrylic acid to the reduced germanium methanol solution produced in + at room temperature.

After reacting for 4 hours with stirring, the solvent is concentrated and removed. Add 1001 rLl of distilled water to this residue! and 1 ml of concentrated HCJ and continue stirring for an additional 4 hours. The solid is collected by filtration to yield 6 g (82% yield 7) of the title compound whose infrared spectrum exactly matches that of the step of Example 1 (also produced in BL).

Production of ruethyl germanium 100 grams of methacrylic acid is added to the methanol solution of reduced germanium produced in step ta+ of Example 15 at room temperature. After reacting for 4 hours with stirring, the solvent is concentrated and removed. 100 d of distilled water is added to this residue and stirring is continued for an additional 4 hours. The solids are collected by filtration to give 3 g (68% yield) of the title compound, identical to that produced in Example 2 by infrared filtration.

Example 17 Bis-β-cal sesquioxide from crotonic acid, Hoxy α
-Production of methyl ethyl germanium, 10% of crotonic acid was added to the reduced methanol solution of dermanium produced in step ta+ of Example 15 at room temperature. ! Add 7. After reacting for 4 hours with stirring, the solvent is concentrated and removed. 100 ml of distilled water is added to this residue and stirring is continued for a further 4 hours. The solid was collected by filtration and the title compound 4.5.9 whose infrared spectrum was identical to that produced in Example 5 (62% yield)
occurs.

Example 18 Preparation of bis-β-carboquine ethyl germanium sesquioxide from acrylonitrile, step fa of Example 15
Acrylonitrile 5I is added to the methanol solution of reduced germanium produced in step 1 at room temperature. After reacting for 4 hours with stirring, solvent 1 is removed by concentration. Add 100 g of distilled water to this residue and continue stirring for an additional 4 hours. The solids were collected by filtration and used in Example 1.
The title compound 5. has exactly the same infrared spectrum as that produced in step fbl. F (yield 69%) is obtained.

Example 19 Bis-β-carboxy sesquioxide from acrylamide
Ethyl rmanium production, step (a) of Example 15
Acrylamide 7.4y is added to the methanol solution of reduced germanium produced in step 1 at room temperature. While stirring 4
After reacting for a period of time, the solvent is removed by concentration. Add 100 g of distilled water to the residue and continue stirring for an additional 4 hours. Collect the solids by filtration and proceed to step t of Example 1.
The title compound 19' (yield 60.5%) is obtained whose infrared spectrum is completely identical to that produced in b+.

Example 20 +a+ Production of methanolic reduced germanium aqueous solution.

Dissolve 49.2 g of Gecz in 70 g of methanol.

57nl of 50% hypophosphorous acid! methanol containing 10
Add 0 ml to this solution. After stirring for 2 hours, the mixture is ready for further use.

6.2 g of acrylic acid is added to the methanolic reduced germanium aqueous solution produced in (bl Production of bis-β'-carboxyethyl germanium sesquioxide from acrylic acid, step ta) above at room temperature. After reacting for 4 hours with stirring, the solvent is removed by concentration. 100 m/distilled water is added to this residue and stirring is continued for a further 4 hours. Filter the formed crystals,
The title compound 3. exhibits an infrared spectrum identical to the product of step tb+ of Example 1. ! i! (yield 42%).

Example 21, Bis-β-carboxy-β sesquioxide from methacrylic acid
-Methyl Ethyl Germanium Production 10 ml of methacrylic acid is added to the methanolic reduced germanium aqueous solution produced in step (a) of Example 20 at room temperature. After reacting for 4 hours with stirring, the solvent is removed by concentration. 100 Tnl of distilled water are added to this residue and stirring is continued for a further 4 hours. The formed crystals are filtered to obtain 4 g (50% yield) of the title compound whose infrared spectrum is exactly identical to the product of Example 2.

Example 22 Bis-β-carboxy-α- sesquioxide from crotonic acid
Production of methyl ethyl germanium 10 g of crotonic acid is added to the methanolic reduced germanium aqueous solution produced in step tal of Example 20 at room temperature. After 4 hours of reaction with stirring, the solvent is evaporated. 100 ml of distilled water is added to this residue and stirring is continued for a further 4 hours.

The crystalline product was filtered to give the title compound 3. whose infrared spectrum was exactly identical to that of Example 5. ! 9 (yield 68
h).

Example 26 Bis-β-carboxy sesquioxide from acrylamide
Production of ethyl germanium, step (a) of Example 20
7.4 g of acrylamide is added to the methanolic reduced germanium aqueous solution produced in step 1 at room temperature. After reacting for 4 hours with stirring, the solvent is evaporated. Add 1007 fLl of distilled water to this residue and continue stirring for an additional 2 hours. The resulting mixture was diluted with 1001 nI of ether! 6 times and then the ether is removed by evaporation.

Add 100 ml of distilled water to this residue again and add 4 more ml of distilled water.
Continue stirring for an hour. The crystalline product is filtered to obtain 5 g (yield 69 g) of the title compound whose infrared spectrum is exactly identical to that of the step of Example 1 (bl).

Example 24 Ethanolic kermanium tetrachloride is reduced with hypophosphorous acid and further reacted with acrylic acid.

Hypophosphorous acid 1.25 mJ (1,59) and ethanol 2
5m1! and then add 2.6 g of germanium tetrachloride. 1.54 g of acrylic acid after stirring for 2 hours
Add. While stirring the resulting mixture, place it in a water bath (7
0°C) for 2 hours. After removing the ethanol by evaporation, 10 ml of distilled water are added and stirring is continued for a further 4 hours at room temperature.

The crystalline product was separated from each other to obtain bis-β-carboxyethyl germanium sesquioxide 0.39 (yield 16%) whose infrared absorption showed the same results as in step tbl of Example 1.
get.

Example 25 Germanium tetrachloride in acidic ethanol is reduced with hypochlorous acid and further reacted with acrylic acid. 1.25 mJ (L5 g) of hypophosphorous acid at 50% in 25 ml of ethanol containing concentrated H (42 ml) and then 2.3 g of germanium tetrachloride in 10 ml of ethyl alcohol.
9,! Add a solution containing 9. After stirring for 2 hours, 1.54 g of acrylic acid is added and stirring is continued for a further 2 hours. After the ethanol has been removed by evaporation, 10 m7 of distilled water are added to the residue and stirred for 4 hours at room temperature. The crystallized product was collected from house to house and the infrared spectrum of bis-β-carboquinethyl germanium sesquioxide 0.8,!
i' (yield: 44 cm).

Example 26 Ethanolic germanium tetrachloride is reduced with sodium hypophosphite and further reacted with acrylic acid, 2.6 sodium hypophosphite in 20 ml of ethanol.
Suspend I. Gθci in 10ml of ethanol,
2.3 Add solution containing j9 dropwise. After stirring for 2 hours, the precipitated product is distributed. Add 1.54 g of acrylic acid to the lachrymal fluid and continue stirring at room temperature for an additional 4 hours. After evaporating the ethanol, 10 ml of distilled water was added to the residue and the residue was hydrolyzed to obtain 0.5 g of bis-β-carboxyethyl germanium sesquioxide (yield 27.5%). The infrared absorption spectrum is the same as in the process of Example 1 (bl).

Example 27 Germanium tetrachloride in acidic ethanol is reduced with sodium hypophosphite and further reacted with acrylic acid. Ethanol containing 1Hcf2 20rrLI! Add 2.6 g of sodium hypophosphite to the solution. The mixture is stirred for 1/2 hour and the precipitate formed is removed by filtration. Add an ethanolic solution containing 2.6 g of germanium tetrachloride and stir for 2 hours. Then add 1.549 g of acrylic acid and continue stirring for a further 4 hours. Evaporate the ethanol and add 10 mf of distilled water to hydrolyze the residue. Crystalline product, bis-β-carzoxyethyl germanium sesquioxide 0
．． 4. F (22% yield) is collected by filtration. The infrared spectrum is the same as that in the process of Example 1 (bl).

Agent Asa Mura Hao 4 other people

Claims (9)

[Claims] (1) A step for producing an organogermanium sesquioxide derivative having the following formula (2), RIR2 (wherein R1 and R2 are independently hydrogen or lower alkyl), (1) optionally in the presence of hydrochloric acid, lower alcohols, or mixtures thereof, either by themselves or
Alternatively, germanium tetrachloride is reduced by contacting with hypophosphorous acid generated in situ from the salt, and then beaten.Then, the reaction mixture is mixed with the following formula (1) % formula % (1) [wherein R1 and R2 is the same as the above definition, and Y is 0OOHXC! OOR (R is lower alkyl)
, CONH2 or CN, and hydrolyzing the product of step (11) to produce the compound of formula (2). A manufacturing method characterized by: (2) In step (1), germanium tetrachloride in hydrochloric acid,
characterized by contacting with sodium hypophosphite,
The method described in paragraph (1) above. (3) In step (1), the step (1) is characterized in that germanium tetrachloride is brought into contact with the aqueous hypophosphorous acid itself.
The method described in section 1). (4) The method according to item (1), wherein in step (1), germanium tetrachloride is brought into contact with sodium hypophosphite in methanol or ethanol. (5) The method according to item (1), wherein in step (1), germanium tetrachloride is brought into contact with aqueous hypophosphorous acid in methanol or ethanol. (6) The method according to item (1), wherein in step (1), germanium tetrachloride is brought into contact with aqueous hypophosphorous acid, methanol or ethanol, and hydrochloric acid. (7) characterized in that step (1) is carried out at reflux temperature;
The method according to item (1) above. (8) The method according to item (]) above, wherein (1) is acrylic acid. (9) The method according to item (1) above, wherein (1) is methacrylic acid. (Ice (1) is methyl methacrylate, the method according to paragraph (1) above. αυ (1) is methyl acrylate, the method according to paragraph (1) above. The method according to item (1), characterized in that o4(1) is crotonic acid. The method according to item (1), characterized in that α3(1) is acrylonitrile. The method described in Section 1. ◇ characterized in that Yu (1) is acrylamide,
The method according to item (1) above. The method according to item (1), characterized in that the αυ process is carried out in the presence of water. The method according to item (1) above, wherein the αQ step +m+ is carried out in the presence of water and hydrochloric acid.